Glucagon-like peptide-1 receptor agonists and glycemic management in non-critical hospitalized patients / 中华内分泌代谢杂志

In recent years, with the continuous development of glucagon-like peptide-1 receptor agonists(GLP-1RA), its role in the management of blood glucose in hospitalized patients has been explored. GLP-1RA can not only control blood glucose in non-critically ill hospitalized patients, but also inhibit appetite, delay gastric emptying, protect nerves, anti-inflammation, reduce systolic blood pressure and blood lipids. At the same time, many studies have found that it can also improve cardiovascular and renal outcomes and reduce the risk of hospitalization complications. Therefore, this paper analyzes the role of GLP-1RA in glycemic management by reviewing domestic and international studies, consensus and guidelines related to inpatient blood glucose management, and helps to better manage blood glucose of patients in non-critical care setting.

Mining and analysis of glucagon-like peptide- 1 receptor agonists related adverse drug reaction signals based on openFDA database / 中国药房

OBJECTIVE To mine and analyze the risk signal of glucagon- like peptide -1 receptor agonists （GLP-1RA）related adverse drug reaction （ADR）. METHODS ADR data related to GLP- 1RA from April 1，2005 to October 16，2021 in the openFDA database were collected ，and the Bayesian confidence propagation neoral network （BCPNN）method was used for data mining. ADR were classified and described by using systematic organ classification （SOC）of drug ADR terminology set in 24.0 edition of MedDRA. RESULTS & CONCLUSIONS A total of 175 719 ADR reports related to GLP- 1RA were retrieved ，with 140 ADR positive signals ，involving five drugs such as exenatide （77 027 cases of ADR and 31 ADR positive signals ），dulaglutide （45 329 cases of ADR and 26 ADR positive signals ），liraglutide （42 748 cases of ADR and 32 ADR positive signals ）， semaglutide（8 844 cases of ADR and 27 ADR positive signals ）and lixisenatide （1 771 cases of ADR and 24 ADR positive signals）. According to SOC classification ，GLP-1RA-induced ADR involved gastrointestinal system ，hepatobiliary system ，nervous system，urinary and renal system ，endocrine system ，immune system and administration site. In the gastrointestinal system ，the risk of （acute）pancreatitis was higher ，and the order of risk was liraglutide ＞exenatide＞semaglutide＞dulaglutide＞lixisenatide； ADR signal of hepatobiliary system was stronger for cholelithiasis ，and the order of risk was liraglutide ＞semaglutide＞exenatide＞ lixisenatide＞dulaglutide. In the nervous system ，the risk of taste disorder was higher ；compared with dulaglutide and lixisenatide ， liraglutide，exenatide and semaglutide were more likely to cause headache and dizziness. In urinary and renal system ， compared with exena tide，dulaglutide and lixisenatide ，liraglutide and semaglutide were more likely to cause acute renal injury. In the endocrine system ，the risk of hypoglycemia was higher ，and the order of risk was exenatide ＞liraglutide＞lixisenatide＞ semaglutide＞dulaglutide. In the immune system ，lixisenatide was more likely to develop urticaria than other drugs ，dulaglutide and liraglutide did not caused ADR signal. Among the administration sites ，the risk of ADR caused by exenatide and dulaglutide was higher，while the risk of related ADR caused by semaglutide was lower. When using GLP- 1RA clinically ，we should closely monitor the renal function and blood glucose of patients ，and pay attention to patients with sudden upper abdominal pain ；in case of relevant ADR ，timely intervention measures should be taken to ensure the safety and effectiveness of medication.

Progress in research on the effects of different glucagon-like peptide-1 receptor agonists on bone metabolism / 中国临床药理学与治疗学

Osteoporosis is one of the common complications of type 2 diabetes mellitus (T2DM). Recent studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1RAs) can promote bone formation and inhibit bone resorption, suggesting that this hypoglycemic drugs may benefit T2DM patients with osteoporosis and high fracture risk, but its underlying mechanism is not fully understood, and different GLP-1RAs exhibit different skeletal effects and molecular mechanisms. In this paper, the effects of several GLP-1RAs on bone metabolism are reviewed.

Effects of Incretin - based Therapy on High - sensitivity C - reactive Protein in Patients with Type 2 Diabetes: A Systematic Review and Meta - Analysis

ABSTRACT Background: Recently, studies had shown that incretin-based therapies could reduce the levels of pro-inflammatory markers. The data on the effects of incretin-based therapies on serum high-sensitivity C-reactive protein (hs-CRP) in type 2 diabetes (T2DM) were inconsistent. Objective: The objective of the study was to assess the effects of incretin-based therapies on hs-CRP in patients with T2DM by meta-analysis. Methods: We searched PubMed, EMBASE, the Cochrane Collaboration Library, and Web of Science to identify the eligible randomized clinical trials until August 2019. The pooled standard mean differences (SMD) were calculated by random-effects model using STATA 11.0. Results: Twenty-five studies with 28 randomized controlled trials were finally included into the meta-analysis. Meta-analysis revealed a significant reduction in hs-CRP following treatment with incretin-based regimens compared to controls (SMD = −0.452, p < 0.001). Subgroup analysis of different class of incretin-based drugs showed that therapy with both dipeptidyl peptidase 4 inhibitors (DPP-4Is, SMD = −0.338, p = 0.026) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs, SMD = −0.544, p = 0.003) caused significant reductions in hs-CRP. Besides, there was a significant reduction in hs-CRP with an intervention duration more than 24 weeks (SMD = −0.465, p = 0.001), while no significant difference with <24 weeks. Meta-regression analyses showed that better glycemic control and more body mass index (BMI) decline were associated with hs-CRP reduction after incretin-based therapies. Conclusions: This meta-analysis suggests that incretin-based therapies, both GLP-1 RAs and DPP-4Is, can cause a significant reduction in hs-CRP in patients with T2DM, which is related to long intervention duration, better glycemic control, and more BMI decline.

Effects of Incretin-based Therapies on Weight-related Indicators among Patients with Type 2 Diabetes: A Network Meta-analysis / 生物医学与环境科学（英文）

Objective@#To evaluate the effects of incretin-based therapies on body weight as the primary outcome, as well as on body mass index (BMI) and waist circumference (WC) as secondary outcomes.@*Methods@#Databases including Medline, Embase, the Cochrane Library, and clinicaltrials.gov (www.clinicaltrials.gov) were searched for randomized controlled trials (RCTs). Standard pairwise meta-analysis and network meta-analysis (NMA) were both carried out. The risk of bias (ROB) tool recommended by the Cochrane handbook was used to assess the quality of studies. Subgroup analysis, sensitivity analysis, meta-regression, and quality evaluation based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) were also performed.@*Results@#A total of 292 trials were included in this study. Compared with placebo, dipeptidyl-peptidase IV inhibitors (DPP-4Is) increased weight slightly by 0.31 kg [95% confidence interval ( ): 0.05, 0.58] and had negligible effects on BMI and WC. Compared with placebo, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) lowered weight, BMI, and WC by -1.34 kg (95% : -1.60, -1.09), -1.10 kg/m (95% : -1.42, -0.78), and -1.28 cm (95% : -1.69, -0.86), respectively.@*Conclusion@#GLP-1 RAs were more effective than DPP-4Is in lowering the three indicators. Overall, the effects of GLP-1 RAs on weight, BMI, and WC were favorable.

A Review of the Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Lean Body Mass in Humans

Weight loss is an important goal in the management of several chronic conditions, including type 2 diabetes mellitus, and pharmacological therapies that aid weight loss are appealing. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) are novel glucose-lowering therapies that have been shown to induce clinically significant reductions in body weight. However, this weight loss may not be attributed solely to fat mass (FM). Given the importance of skeletal muscle and lean body mass (LBM) on cardio-metabolic health and physical function, we reviewed the available literature reporting the effects of GLP-1RAs and SGLT2is on body composition. Results demonstrate that, in most circumstances, the weight loss associated with both therapies predominantly comprises a reduction in FM, although significant heterogeneity exists between studies. In over half of the studies identified, the proportion of LBM reduction ranged between 20% and 50% of total weight lost, which is consistent with diet-induced weight loss and bariatric surgery. No clear differences existed between GLP-1RAs and SGLT2is. Consequently, the loss of LBM and skeletal muscle associated with weight loss induced by GLP-1RAs and SGLT2is warrants attention. Strategies to preserve skeletal muscle and improve physical function, for example through structured exercise, are of great importance.

The review of the effects of glucagon-like peptide-1 and glucagon-like peptide-1 receptor agonists on hypothalamus-pituitary-gonad axis / 中华内分泌代谢杂志

Mammalian reproduction is closely related to their metabolic status. The hypothalamus-pituitary-gonad axis ( HPG axis) is regulated by various metabolic factors. Glucagon-like peptide-1 ( GLP-1) is one of various metabolic factors that not only affect glycemic and metabolic control, but also with many other effects, including affecting HPA axis. The function of GLP-1 is related to the location of glucagon-like peptide-1 receptor ( GLP-1R) distribution. It has been confirmed that GLP-1R is widely distributed in HPG axis. The effects of GLP-1 and GLP-1R agonists on the HPG axis have also attracted much attention. The positive effects of GLP-1 and GLP-1R agonists on the HPG axis indicated it could be the new target for the new treatment for gonadal diseases. The role of GLP-1 and GLP-1R agonists in the central nervous system is reviewed.

Efectos cardiovasculares de los nuevos fármacos no insulínicos en diabetes / Cardiovascular effects of new non-insulinic anti-diabetes drugs]

La diabetes mellitus constituye actualmente un grave problema de salud pública a nivel mundial, que incrementa el riesgo de presentar complicaciones tanto microvasculares como macrovasculares. Aunque lograr los objetivos de glucemia recomendados reduce el riesgo de complicaciones microvasculares, el efecto de los fármacos para tratar la hiperglucemia sobre las complicaciones macrovasculares y la muerte cardiovascular es motivo de preocupación. En este contexto, las agencias regulatorias han modificado la normativa para la aprobación de nuevos fármacos en diabetes, de forma que establecen la necesidad de demostrar que son capaces de disminuir la glucemia junto con una evaluación sólida de la seguridad cardiovascular. El objetivo de este trabajo es revisar los efectos cardiovasculares de las nuevas familias de fármacos no insulínicos, en especial en su efecto sobre el riesgo de eventos cardiovasculares mayores. En los últimos años, finalmente, se ha confirmado que algunos fármacos para tratar la diabetes no solo son seguros desde el punto de vista cardiovascular, sino que incluso han mostrado capacidad para reducir el riesgo de enfermedad cardiovascular en la diabetes mellitus tipo 2. La evidencia obtenida ha determinado la actualización de algunas guías terapéuticas vigentes cuando el riesgo cardiovascular debería considerarse una variable fundamental al momento de la elección terapéutica en pacientes con diabetes.

Diabetes mellitus is currently a serious public health problem worldwide, that increases the risk of presenting microvascular and macrovascular complications. Although achieving the recommended blood glucose goals reduces the risk of microvascular complications, the effect of the drugs used to treat hyperglycemia on macrovascular complications and cardiovascular death is a cause for concern. In this context, the regulatory agencies have modified the regulations for the approval of new drugs in diabetes, by adding the need to demonstrate that they are capable of lowering blood glucose levels together with a solid assessment of cardiovascular safety. The objective of this study is to review the cardiovascular effects of the new families of non-insulin drugs, with special emphasis on their effect on the risk of major cardiovascular events. In recent years, it has finally been confirmed that some of the drugs used to treat diabetes are not only safe from a cardiovascular point of view, but have even shown capacity to reduce the risk of cardiovascular disease in type 2 diabetes mellitus. The evidence obtained determined the updating of some current therapeutic guidelines when cardiovascular risk should be considered a fundamental variable at the time of therapeutic choice in patients with diabetes.

New anti-diabetic agents

Diabetes mellitus is characterized by hyperglycemia due to insulin deficiency and/or insulin resistance. Cardiovascular disease (CVD) is a major comorbidity of type 2 diabetes mellitus, and is the most common cause of death in people with diabetes mellitus. Several clinical trials have addressed the long-term effects of near-normoglycemia on CVD, but did not find evidence of an effect. However, some recent clinical trials of sodium glucose cotransporter 2 inhibitors (EMPA-REG [Empagliflozin Cardiovascular Outcomes and Mortality in Type 2 Diabetes Trial], CANVAS [Canagliflozin Cardiovascular Assessment Study]) or glucagon-like peptide-1 agonists (LEADER [Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term Evaluation], SUSTAIN-6 [Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes]) showed very promising results regarding the prevention of CVD. In this review, I discuss some of these new anti-diabetic agents and present clinical information regarding these drugs.

Individualized, patient-centered use of lixisenatide for the treatment of type 2 diabetes mellitus / 中华内分泌代谢杂志

This review discussed the role of gastric emptying and its related glucagon-like peptide-1(GLP-1) releasing in maintaining glucose homeostasis, and further illustrated the efficacy and safety of short-acting GLP-1 receptor agonists( GLP-1 RAs) ,such as Lixisenatide in treating type 2 diabetes. The cardiovascular effects of GLP-1 RAs were also reviewed. This article is the Chinese translation of "Individualized, patient-centered use of lixisenatide for the treatment of type 2 diabetes mellitus"[Expert Opin Drug Metab Toxicol, 2017,13(3):311-321]which was published in March 2017, with the permission from the journal(Taylor&Francis Group).

A meta-analysis of cardiovascular safety of GLP-1 receptor agonists for diabetes / 中国药学杂志

OBJECTIVE: To evaluate the cardiovascular safety of glucagon-like peptide-1 receptor agonists (GLP-1 RA) for diabetes systematically. METHODS: Medline, Embase, ClinicalTrails. gov, Cochrane Liabrary, CBM, and CNKI were retrieved to collect all the randomized controlled trials (RCT) with a duration of at least 24 weeks, comparing a GLP-1 RA with a non-GLP-1 RA agent in type 2 diabetes, and then a Meta-analysis was performed with RevMan5.3 software. RESULTS: Fifty-one RCTs, invovling 26140 individuals with type 2 diabetes, were included in the analysis. The difference in the incidence of major adverse cadiovascular events (MACE) between GLP-1 RA and comparators did not reach statistical significance, and the odds ratio was 0.78 (0.57, 1.08), although a favorable trend was observed; while in comparisons with placebo, the incidence of MACE was significantly decreased and the odds ratio was 0.5 (0.28, 0.87); compared with comparators, a significant decrease of the incidence of all-cause and cardiovascular mortality were detected and the odds ratio were 0.53 (0.27, 0.93) and 0.38 (0.16, 0.90), respectively. As for the cardiovascular risk factors, GLP-1 RA significantly decreased the HbA1c, weight, TG, LDL, SBP, but increased the heart rates. CONCLUSION: GLP-1 RA may have a protective effect on cardiovascular diseases, compared with the comparators, especially compared with placebo.

The Role of Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes: Understanding How Data Can Inform Clinical Practice in Korea

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce glycosylated hemoglobin (HbA1c, 0.5% to 1.0%), and are associated with moderate weight loss and a relatively low risk of hypoglycemia. There are differences between Asian and non-Asian populations. We reviewed available data on GLP-1RAs, focusing on Korean patients, to better understand their risk/benefit profile and help inform local clinical practice. Control of postprandial hyperglycemia is important in Asians in whom the prevalence of post-challenge hyperglycemia is higher (vs. non-Asians). The weight lowering effects of GLP-1RAs are becoming more salient as the prevalence of overweight and obesity among Korean patients increases. The higher rate of gastrointestinal adverse events amongst Asian patients in clinical trials may be caused by higher drug exposure due to the lower body mass index of the participants (vs. non-Asian studies). Data on the durability of weight loss, clinically important health outcomes, safety and optimal dosing in Korean patients are lacking. Use of GLP-1RAs is appropriate in several patient groups, including patients whose HbA1c is uncontrolled, especially if this is due to postprandial glucose excursions and patients who are overweight or obese due to dietary problems (e.g., appetite control). The potential for gastrointestinal adverse events should be explained to patients at treatment initiation to facilitate the promotion of better compliance.

The role of glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease / 中华内分泌代谢杂志

Glucagon-like peptide-1 (GLP-1) receptor agonists are incretin-based drugs for type 2diabetes.In recent years,it has been proven in clinical practices that GLP-1 receptor agonists have protection effect beyond anti-hyperglycemic effects,such as improvement of non-alcoholic fatty liver disease (NAFLD).The cogent evaluation,understanding,and exploration of therapeutic effect and mechanism of GLP-1 receptor agonists in NAFLD are important.Besides,it would be of great significance to identify pathogenesis of diabetes,its correlation with NAFLD,and the development of new drugs.This article briefly reviews the therapeutic effect of GLP-1 receptor agonists on NAFLD.